The degradation of lipid by molecular oxygen has been suggested to be involved in diverse pathologies. Heart attack, stroke, the allergic response, inflammatory disease, the response to toxic xenobiotics, cancer, and the aging process have all been linked in one way or another to the reaction of lipid with molecular oxygen. The random reaction of lipid and oxygen, lipid peroxidation, is a complex free radical process that is poorly understood from a chemical viewpoint. One major aspect of the research proposed here is to develop a mechanistic understanding of lipid peroxidation. In this regard, oxidation mechanisms of highly unsaturated fatty acids and phospholipid will be studied in organic solvent and in model membranes. Specific aims of this research relate to: (1) understanding the nature of the addition of oxygen to carbon radicals derived from unsaturated fatty acids (2) examining the effect of lipid-soluble and water-soluble anti-oxidants on the distribution of products of autoxidation of phospholipid model membranes (3) utilizing mercury based cyclization reactions to study carbon-radicals thought to be important in peroxidation (4) developing microbore HPLC techniques for the analysis of complex lipid mixtures (5) analyzing biological mixtures for the purpose of detecting in vivo lipid peroxidation and developing a peroxidizability index of natural lipid sources such as erythrocyte and mitochondrial membranes. A second major thrust of the proposed research is to focus on organic chemical reactions in organized media such as lipid bilayers or model membranes. Preliminary results suggest that lipid bilayers may affect stereochemical control of organic reactions and the concept of lipid liquid-crystalline control of organic stereochemistry is one that deserves serious consideration. Several types of reactions will be examined in model membranes (liposomes) prepared from synthetic phosphatidylcholines. In particular, the following cases will be examined (1) diastereomeric differentiation in fragmentation reactions (2) diastereoselective reactions from radical coupling (3) stereoselective reactivity due to the chiral field of phospholipid head-groups (4) chiral selective membrane passive transport (5) diastereoselective bond-making reactions. In consideration of a lipid bilayer as solvent for organic reactions, a host of reactions can be considered for study. The emphasis of all this work is "What is the effect, if any, of a liquid-crystalline amphipathic solvent on the reactivity and selectivity of organic reactants?"